Control of bacterial infection may ultimately require an ability to manipulate the immune system to enhance its protective effects. Toward this end and toward improved management of deficiencies of the immune system and diseases caused by the undesirable effects of inflammation, the investigations proposed here seek information about the normal mechanisms of resistance to bacterial infection. The interaction of bacteria and specific and "natural" antibodies, complement activated through the classical and alternate pathways, and polymorphonuclear phagocytes will be studied in vitro in the following specific projects: (1) Studies of the function of the alternate complement pathway in defense against bacteria and the role of the spleen in that function. Enhancement of phagocytosis (opsonization) through the alternate pathway will be studied in serum from newborn infants and patients with sickle cell disease or previous splenectomy. Attempts will be made to compare the patient's experience with bacterial infection and the ability of his serum to promote phagocytosis through the alternate pathway, and to identify factors deficient in abnormal sera. The requirements for and kinetics of opsonization through the alternate pathway will be studied, and an animal model for the role of the spleen in producing properdin system factors will be sought. (2) Studies of the mechanism of bacterial killing by phagocytes. The relationship between superoxide anion, peroxide, and myeloperoxidase and phagocytic bactericidal activity in polymorphonuclear leukocytes will be studied. The possible release of these agents upon stimulation by factors of the complement system will be explored. The effect of sulfonamides on in vitro leukocyte function and resistance to bacterial infection in patients with chronic granulomatous disease will be studied. (3) Studies of the opsonizing antibody response to H. influenzae and pneumococcal otitis media in children. Correlations between serum opsonizing antibody, age, and recurrence of infection will be made.